Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3213 | 9862;9863;9864 | chr2:178766447;178766446;178766445 | chr2:179631174;179631173;179631172 |
| N2AB | 3213 | 9862;9863;9864 | chr2:178766447;178766446;178766445 | chr2:179631174;179631173;179631172 |
| N2A | 3213 | 9862;9863;9864 | chr2:178766447;178766446;178766445 | chr2:179631174;179631173;179631172 |
| N2B | 3167 | 9724;9725;9726 | chr2:178766447;178766446;178766445 | chr2:179631174;179631173;179631172 |
| Novex-1 | 3167 | 9724;9725;9726 | chr2:178766447;178766446;178766445 | chr2:179631174;179631173;179631172 |
| Novex-2 | 3167 | 9724;9725;9726 | chr2:178766447;178766446;178766445 | chr2:179631174;179631173;179631172 |
| Novex-3 | 3213 | 9862;9863;9864 | chr2:178766447;178766446;178766445 | chr2:179631174;179631173;179631172 |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs760666570  |
0.232 | 0.993 | N | 0.481 | 0.253 | 0.0806252709748 | gnomAD-2.1.1 | 1.99E-05 | None | None | None | None | N | None | 0 | 1.44592E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/R | rs760666570 |
0.232 | 0.993 | N | 0.481 | 0.253 | 0.0806252709748 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | rs760666570 |
0.232 | 0.993 | N | 0.481 | 0.253 | 0.0806252709748 | gnomAD-4.0.0 | 4.33729E-06 | None | None | None | None | N | None | 0 | 1.16682E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1251 | likely_benign | 0.1082 | benign | -0.26 | Destabilizing | 0.807 | D | 0.339 | neutral | None | None | None | None | N |
| S/C | 0.3243 | likely_benign | 0.3203 | benign | -0.281 | Destabilizing | 0.999 | D | 0.505 | neutral | N | 0.430842846 | None | None | N |
| S/D | 0.5152 | ambiguous | 0.5176 | ambiguous | 0.068 | Stabilizing | 0.953 | D | 0.359 | neutral | None | None | None | None | N |
| S/E | 0.644 | likely_pathogenic | 0.6311 | pathogenic | -0.039 | Destabilizing | 0.953 | D | 0.366 | neutral | None | None | None | None | N |
| S/F | 0.4629 | ambiguous | 0.4533 | ambiguous | -0.912 | Destabilizing | 0.993 | D | 0.629 | neutral | None | None | None | None | N |
| S/G | 0.157 | likely_benign | 0.1472 | benign | -0.34 | Destabilizing | 0.939 | D | 0.349 | neutral | N | 0.390280088 | None | None | N |
| S/H | 0.5869 | likely_pathogenic | 0.5799 | pathogenic | -0.736 | Destabilizing | 0.999 | D | 0.486 | neutral | None | None | None | None | N |
| S/I | 0.3724 | ambiguous | 0.3341 | benign | -0.184 | Destabilizing | 0.982 | D | 0.609 | neutral | N | 0.392915368 | None | None | N |
| S/K | 0.8555 | likely_pathogenic | 0.8657 | pathogenic | -0.442 | Destabilizing | 0.953 | D | 0.365 | neutral | None | None | None | None | N |
| S/L | 0.2026 | likely_benign | 0.1832 | benign | -0.184 | Destabilizing | 0.91 | D | 0.473 | neutral | None | None | None | None | N |
| S/M | 0.3382 | likely_benign | 0.2925 | benign | 0.006 | Stabilizing | 0.999 | D | 0.483 | neutral | None | None | None | None | N |
| S/N | 0.2323 | likely_benign | 0.1987 | benign | -0.165 | Destabilizing | 0.939 | D | 0.397 | neutral | N | 0.36917747 | None | None | N |
| S/P | 0.5509 | ambiguous | 0.527 | ambiguous | -0.183 | Destabilizing | 0.993 | D | 0.489 | neutral | None | None | None | None | N |
| S/Q | 0.6926 | likely_pathogenic | 0.676 | pathogenic | -0.429 | Destabilizing | 0.993 | D | 0.417 | neutral | None | None | None | None | N |
| S/R | 0.7961 | likely_pathogenic | 0.8201 | pathogenic | -0.167 | Destabilizing | 0.993 | D | 0.481 | neutral | N | 0.390546278 | None | None | N |
| S/T | 0.1093 | likely_benign | 0.1014 | benign | -0.291 | Destabilizing | 0.079 | N | 0.193 | neutral | N | 0.427881422 | None | None | N |
| S/V | 0.3685 | ambiguous | 0.3171 | benign | -0.183 | Destabilizing | 0.91 | D | 0.453 | neutral | None | None | None | None | N |
| S/W | 0.4907 | ambiguous | 0.5473 | ambiguous | -0.946 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| S/Y | 0.3744 | ambiguous | 0.403 | ambiguous | -0.656 | Destabilizing | 0.998 | D | 0.623 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.